tbuckley/cabot-search huggingface dataset:
P1321: CLINICAL ANALYSIS OF THE RELATIONSHIP BETWEEN PLASMA SC5B-9 LEVEL AND TRANSPLANTATION-ASSOCIATED THROMBOTIC MICROANGIOPATHY (TA-TMA) IN PEDIATRIC PATIENTS
Authors: Linlin Luo, Ming Sun, Hao Xiong
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Clinical Analysis of the relationship between plasma sC5b-9 level and transplantation-associated thrombotic microangiopathy (TA-TMA) in pediatric patients Aims: To investigate the association between dynamic changes in plasma human terminal complement complex C5b-9 (sC5b-9) concentration level and hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. Methods: Retrospective analysis of clinical data of regular dynamic detection of plasma sC5b-9 concentration for predicting TA-TMA after allo-HSCT performed at the Department of Hematology-Oncology, Wuhan Children’s Hospital from May 2020 to May 2022. Results: 74 children with complete clinical data were included in the study. The median age was 6 (3.1-10.6) years and 42 (56.7%) cases were male. The primary diseases were mainly aplastic anemia in 26 (35.1%) cases, acute myeloid leukemia in 23 (31.1%) cases, and β-thalassemia in 9 (12.1%) cases. The median time of onset was 83 (56-120) days after transplantation in 17 (14.7%) patients with TA-TMA, including 10 (62.5%) with early-onset TA-TMA and 7 (37.5%) with late-onset TA-TMA. 1-year OS was (34.3±11.8)% in children with TA-TMA and (96.4±2.5)% in children with non-TA-TMA. (2.5)%, with a statistically significant difference (χ2 =31.46, P<0.05). Comparison of sC5b-9 levels before and after transplantation in children with TA-TMA showed a correlation between plasma sC5b-9 concentration and TA-TMA prevalence (P < 0.05). Each 1 ng/ml increase in plasma sC5b-9 concentration resulted in a 1.3% increase in the risk of TA-TMA. The discriminative effect, i.e., the maximum area under the curve (AUC), was 0.934 (95% CI=0.872-0.996) when the sC5b-9 concentration was ≥344.67 ng/ml, at which time the sensitivity of the diagnosis of TA-TMA was 94.1% and the specificity was 89.8%. Summary/Conclusion: The plasma sC5b-9 concentration after allo-HSCT in children is closely related to the occurrence of TA-TMA in children, and when plasma sC5b-9≥344.67ng/ml can help clinical diagnosis of TA-TMA. Keywords: Thrombotic microangiopathy, Children, Transcriptional regulation
P1584: PREVELANCE OF ABO DISCPRENACIES AND ITS CLASSIFACTION IN BLOOD DONORS AT REGIONAL BLOOD CENTRE, KARACHI.
Authors: Samra Waheed
Journal: HemaSphere (2023)

Topic: 31. Transfusion medicine Background: ABO and Rh systems are the most important blood group systems of human body. More than 400 blood group systems have been reported, however majority of them are not clinically significant. The ABO group system comprises of antigens represented by forward blood grouping and antibodies represented by reverse blood grouping. Reverse blood grouping is usually done to verify the results of forward blood grouping. ABO discrepancy is defined as a difference of result between forward and reverse group and has been reported to be around 0.15-0.19%. ABO discrepancies are divided into 4 types. Type 1 discrepancy include those having missing antibodies in reverse grouping and are most common. Type 2 discrepancy include missing antigens in forward grouping. Type 3 are those because of abnormalities in plasma or proteins and type 4 is represented as miscellaneous. Aims: The aim of this study was to calculate the frequency of ABO discrepancies in healthy blood donors, its classification into different types and identification of different subgroups in order to provide safe blood to the patients. Methods: Descriptive, cross sectional study was conducted at Regional blood centre Karachi from January 2020 to December 2022. All the blood donors accepted at our centres, were included in the study. 52,568 donors were enrolled in the study. Blood samples were collected in di-potassium ethylene diamine tetra acetic acid (K2 EDTA) and yellow gel top vacutainers. Blood grouping was performed by a technician/ technologist by tube method and was reconfirmed by a senior technologist. Results: 52568 samples were included in the study, with majority of the males. The mean age of blood donors was 28.5 years. ABO discrepancy was found in 92 cases (0.17%). 4 groups of ABO discrepancies were made according to AABB. Most common ABO discrepancy was type 1 (56.5%) followed by type 2 (30.4%). Type 3 and type 4 were 10.9% and 2.2% respectively. Most common blood group associated with ABO discrepancies was O positive, followed by A positive. Moreover, type 1 discrepancy was mostly associated with blood group O and type 3 discrepancy was associated with blood group A, this association was found to be statistically significant. (p value 0.001). Most subgroups were associated with A group. Summary/Conclusion: ABO blood grouping remains the most important testing in the blood donors. The significance of determining the actual blood group lies in the fact that safe blood transfusion should be the utmost priority. Complete blood grouping along with resolution of discrepancies will continue to be a significant feature in providing safe blood to the patients and preventing them from fatal transfusion reactions.Keywords: ABO blood group
P1543: CHARACTERISTICS AND OUTCOMES OF PATIENTS WITH HEMATOLOGICAL MALIGNANCIES THAT NEED VASOACTIVE SUPPORT – SINGLE CENTER STUDY
Authors: Roy Vitkon, Noa Halak, Irit Avivi
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: The prognosis of patients (pts) with hematological malignancies (HM) that develop a hemodynamic shock (HS) following treatment, requiring treatment with vasoactive agents, is considered to be relatively poor. However, limited data exist on pts that were treated during the last decade, especially for those treated outside intensive care unit (ICU), in the hemato-oncological department. Aims: Our study evaluated the characteristics, outcome and risk factors for death, in hemato-oncological pts that developed HS, treated with vasoactive agents in a single hematological department. Methods: All consecutive pts fulfilling the following criteria were included: (i) age≥ 18 years (ii) known HM (iii) admitted to the Hematology department at Tel-Aviv Sourasky Medical Center between 01/2017 and 07/2022 (iv) Diagnosed with HS and treated with vasoactive agents. Medical records were extracted using MD-Clone platform (https://www.mdclone.com). Data on demographics, HM, most recent anti-neoplastic treatment, cause and treatment of HS (including ventilation support), APACHE II and SOFA scores at initiation of vasoactive agent and 30 day mortality rate were recorded. Analysis for factors predicting survival were performed Results: One hundred fifty five out of 1641 pts, admitted to the Hematology department, developed post therapy HS. Table 1 present pts characteristics and outcomes. Median age was 66 years (19-85). The most common HMs were acute leukemia (AL) (42%), followed by lymphoproliferative diseases (41%) and multiple myeloma (MM) (16%). Prior to the development of HS, 47% were treated with allogeneic hematopoietic cell transplantation (Allot), 32% had chemotherapy and 20% received immunotherapy (CART or BITE). At the time of HS median APACHE II and SOFA scores were 20 and 7 respectively. Most pts (71%) developed septic shock, 51% with confirmed bacteremia and 19% had cytokine release syndrome (CRS). Forty-five percent (n=69) required respiratory support, 11% having mechanical ventilation. 30 day mortality rate in the entire cohort was 32%; 38%% in sepsis-induced HS and 7% in CRS-induced shock. Diagnosis of AL, prior non immunotherapy based treatment, refractory HM, septic vs CRS-induced HS, need for mechanical ventilation and high APACHE II and SOFA scores were associated with higher 30 day mortality rates. Summary/Conclusion: Most HM pts that develop post treatment HS are still salvageable and can be treated in hemato-oncological units by experienced hemato-oncology teams. Moreover, CRS-induced HS is almost always reversible and associated with good outcome, whereas septic shock is associated with a poorer survival, especially in patients with active HM and in those requiring mechanical ventilation. APACHE II and SOFA scores can reliably predict survival in patients with non- CRS induced shock.Keywords: Immunotherapy, Sepsis, Real world data, Infection
P1310: HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR HEPATITIS‑ASSOCIATED APLASTIC ANEMIA AND NON‑HEPATITIS‑ASSOCIATED APLASTIC ANEMIA: A PROPENSITY SCORE-MATCHED ANALYSIS
Authors: Jia LI
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Hepatitis-associated aplastic anemia (HAAA) is a rare but known variant of AA (aplastic anemia) in which bone marrow failure follows the development of hepatitis. HAAA accounts for approximately 1-5% of newly diagnosed AA cases. Relatively few studies have focused on the results of different treatments for patients with HAAA. Aims: We aimed to validate the efficacy and safety of hematopoietic stem cell transplantation (HSCT) in HAAA patients and explore the application prospect of haploidentical donor (HID)-HSCT in HAAA patients. Methods: We reviewed 260 patients who underwent HSCT for acquired aplastic anemia and eventually included 30 HAAA patients and 90 non-HAAA patients using propensity score matching. Furthermore, we conducted donor and age-based subgroup analyses of 30 patients diagnosed with HAAA. Results: In the HAAA group, the estimated 5-year overall survival (OS) rate (75.8% vs. 86.5%, P=0.409), failure-free survival (FFS) rate (74.0% vs. 83.2%, P=0.485), GVHD-free, failure-free survival (GFFS) rate (61.2% vs. 67.6%, P=0.669) after HSCT were slightly lower but not statistically significant than those in the non-HAAA group. Both groups did not significantly differ in engraftment, post-transplant severe infection, CMV or EBV viremia, or GVHD incidences. The patterns of immune reconstitution were broadly consistent between the two groups. When stratifying HAAA patients according to donor type, no significant differences in survival, TRM (transplant-related mortality), or GVHD cumulative incidences were observed. CMV viremia (68.7% vs. 8.3%, P=0.009) occurred more commonly in HID transplants than in matched sibling donor (MSD) transplants. However, early CMV disease incidence (5.6% vs. 0.0%, P=1.000) was low. Summary/Conclusion: Overall, the post-transplant outcomes of HAAA patients were comparable to those of non-HAAA patients after balancing potential confounders, and HID-HSCT can offer an alternative curative option for HAAA. Keywords: Allo-SCT, Survival, CMV, Aplastic anemia
P1501: HEP-25/ERFE RATIO AS A SUBSTANTIAL PROGNOSTIC MARKER OF ERYTHROPOIESIS IN DIALYSIS-DEPENDENT PATIENTS
Authors: Salwa Bakr, Karem Salem, Ahmad Rashed, Mohamed E A Tantawy, Asmaa Younis Elsary, Hanan Abdelmoneam Shamardl, Eman Ezzat
Journal: HemaSphere (2023)

Topic: 29. Iron metabolism, deficiency and overload Background: Anemia is one of the commonest clinical feature of chronic kidney disease (CKD). Hepcidin (HEP), a key factor of iron metabolism, regulation in CKD is complex influenced by renal function, iron status, and inflammation. Aims: This study aimed to evaluate the correlations between serum erythropoietin (EPO), erythroferrone (ERFE) and hepcidin (HEP-25) levels, and the utility of HEP-25/ERFE ratio as a predictor of erythropoiesis activity. Methods: This cohort study conducted on 35 patients with anemia related end stage CKD on sustained dose of short-acting erythropoiesis stimulating agent (ESA). Quantitative assessment of EPO, ERFE, and HEP in day zero, 5 and 7 consequently after ESA injection was performed using ELISA technique. Erythropoiesis activity was monitored by noting the increment in reticulocyte parameters between baseline day zero and day7. Results: Out of 35 dialysis-dependent patients, erythropoiesis outcomes were (54.3%) effective, (34.3%) ineffective and (11.4%) accelerated but ineffective. Though there was no significance difference in HEP/ERFE ratio and outcomes of erythropoiesis, the ratio was lower among those with effective than those with ineffective erythropoiesis. Summary/Conclusion: Reticulocyte parameter (RET-He) is a substantial predictor of abnormal iron utility and effectiveness of erythropoiesis in patients with CKD rather than HEP-25/ ERFE ratio. Keywords: Hepcidin, Anemia, Reticulocyte, Erythropoietin
P1527: ASSESSMENT OF RISK FACTORS AND ANTIMICROBIAL THERAPY FOR CARBAPENEM-RESISTANT PSEUDOMONAS AERUGINOSA BLOODSTREAM INFECTIONS IN HEMATOLOGICAL PATIENTS
Authors: Zhangjie Chen, Sisi Zhen, Yuanqi Zhao, Sizhou Feng
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Infections caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) have been linked to increased mortality rates, particularly in patients with hematologic malignancies and those who received allogenic-hematopoietic stem cell transplantation. Aims: This retrospective study aimed to investigate clinical outcomes of CRPA bacteremia, identify associated risk factors and compare effectiveness of traditional and novel antibiotic regimen. Methods: This single-center retrospective study included patients with hematological diseases who were diagnosed with CRPA bacteremia between January 2014 and August 2022. The primary outcome was 30-day all-cause mortality, while secondary outcomes measured 7-day and 30-day clinical cure rates. Multivariable cox regression analysis was performed to identify risk factors associated with 30-day mortality. Results: A total of 100 patients diagnosed with CRPA bacteremia were included, of whom 29 had received allogenic-hematopoietic stem cell transplantation. Among the patients, 24 were treated with ceftazidime-avibactam (CAZ-AVI)-based therapy and 76 with traditional antibiotics. The study reported a 30-day mortality rate of 21.0%. Multivariable cox regression analysis identified neutropenia ≥7 days after BSI (P=0.030, HR: 4.068, 95%CI: 1.146~14.434), higher Pitt bacteremia score (P<0.001, HR:1.824, 95%CI: 1.322~2.517), higher Charlson comorbidity index (P=0.01, HR: 1.613, 95%CI: 1.124~2.315) and bacteremia due to multidrug-resistant Pseudomonas aeruginosa (MDR-PA) (P=0.024, HR:3.086, 95%CI: 1.163~8.197) as independent risk factors for 30-day mortality. After adjusting for confounders, an additional multivariable cox regression analysis revealed that definitive regimens containing CAZ-AVI were associated with lower mortality in CRPA bacteremia (P=0.016, HR: 0.150, 95%CI: 0.032~0.702) and MDR-PA bacteremia (P=0.019, HR: 0.119, 95%CI: 0.020~0.709). Summary/Conclusion: Among patients with hematological diseases and CRPA bacteremia, 30-day mortality rate was 21.0% (21/100). Neutropenia ≥7 days after BSI, higher Pitt bacteremia score, higher Charlson comorbidity index and bacteremia due to MDR-PA significantly increased 30-day mortality. CAZ-AVI-based regimens were found to be effective alternatives for the treatment of bacteremia caused by CRPA or MDR-PA.Keywords: Hematological malignancy, Infection, Stem cell transplant
P1378: CAR-T CELLS TARGETING CD38 AND LMP1 EXHIBIT ROBUST ANTI-TUMOR ACTIVITY AGAINST NK/T-CELL LYMPHOMA
Authors: LI Hongwen, Mingzhi Zhang
Journal: HemaSphere (2023)

Topic: 24. Gene therapy, cellular immunotherapy and vaccination - Biology & Translational Research Background: Natural killer/T-cell lymphoma (NKTCL) is an aggressive lymphoma with poor prognosis. In the past decade, chimeric antigen receptor transduced T (CAR-T) cell therapy has been a promising strategy against hematologic malignancies. Researchers have evaluated the efficacy of CAR-T cell targeting CD38 in multiple myeloma and NKTCL. LMP1 may induce a malignant transformation in B cells and epithelial cells, making it a non-negligible molecule in NKTCL. These suggest the potential clinical administration of CD38 and LMP1 targeting therapy. Aims: We aimed to provide an immunotherapy for clinical practice and improve the treatment efficiency of NKTCL. Methods: Four second-generation CAR-T cells including two single-targeted CAR (CD38-CAR and LMP1-CAR) and two tandem CAR (CD38-LMP1 Tan CAR 1 and Tan CAR 2) were constructed. Then the effects of four CAR-T cells on NKTCL cells were evaluated both in vitro and in vivo. Results: Four CAR-T cells could effectively eliminate malignant target-positive NKTCL cells in vitro. They could be activated and produce inflammatory cytokines in a target-dependent manner. Stimulated by CD38+LMP1+ NKTCL cells, two Tan CAR-T cells produced more IL-13, Granzyme B, IFN-γ and TNF-α than LMP1-CAR-T cells. In vivo test showed that CAR-T cells also exhibit significant anti-tumor effects in a xenotransplant NKTCL mice models. Two Tan CAR-T cells showed higher cytolytic activity against CD38+LMP1+ NKTCL cells than single-targeted CAR-T cells both in vitro and in vivo. Summary/Conclusion: We explored the feasibility of CAR-T cell therapy targeting both CD38 and LMP1 molecule. Our results indicated a promising effective therapeutic strategy for NKTCL. Keywords: Non-Hodgkin’s lymphoma, CD38, EBV, CAR-T
P1491: THE DYNAMIC INTERACTION BETWEEN INFLAMMATION AND THE IRON SENSOR HFE, IN SEVERE MALARIA-INDUCED ANEMIA
Authors: Ana Pêgo, Illyane Lima, Maja Spasic, Antonella Nai, Laura Silvestri, Raffaella Gozzelino
Journal: HemaSphere (2023)

Topic: 29. Iron metabolism, deficiency and overload Background: Severe malarial anemia (SMA) is a complication developed during Plasmodium infection. It is often associated with increased rates of malaria-related morbidity and mortality, especially in children and pregnant women. Hence, it is fundamental to investigate new parameters to prevent this lethality. The occurrence of ineffective erythropoiesis, caused by a dysregulated erythropoietin (EPO)-erythropoietin receptor (EPOR) signaling pathway, is one of the main features of SMA. Aims: Therefore, to gain new insights into the pathogenesis of SMA and to better understand the dynamic interaction between erythropoiesis and inflammation, wild-type and HFE knockout mice were injected with Plasmodium chabaudi chabaudi (Pcc). Methods: Due to the fundamental role of iron in erythropoiesis and immune response activation, the expression of iron sensors, like HFE, was analyzed, detecting a strict correlation with disease severity. With this in mind, the action of HFE in the pathogenesis of SMA and its role on the immune response activation, elicited to combat malaria, was also investigated, and compared to Pcc-infected wild-type animals. Results: Results suggested that the anemic profile, associated with malaria infection, improves in Pcc-induced HFE knockout mice. However, an increased level of pro-inflammatory markers, such as CXCL1, IL-10, and TNF-α, was observed in these animals upon infection, when compared to wild type. The number and activation of peripheral blood leukocytes was assessed by flow cytometry. A higher activation of the immune response was found in HFE-deficient mice in relation to Pcc-induced wild type animals, especially in the first days of infection. The splenomegaly presented by HFE-deficient mice was linked to an enhanced inflammation, which persists along the infection, as demonstrated by the inflammatory profile of analyzed cells. Whether the improved anemia could be caused by a stronger immune response activation of Pcc-induced HFE-knockout mice in relation to wild-type animals, which is coupled to lower parasite counts in the blood, is likely the case. Summary/Conclusion: These findings suggest a potential role for HFE in the pathogenesis of SMA, revealing HFE as a potential target for therapeutic strategies against hemolytic disorders. Keywords: Anemia, Malaria, Inflammation, Infection
P1529: SYSTEMATIC REVIEW OF THE SHORT-TERM VERSUS LONG-TERM DURATION OF ANTIBIOTIC MANAGEMENT FOR NEUTROPENIC FEVER IN PATIENTS WITH HEMATOLOGICAL MALIGNANCY
Authors: Kazuhiro Ishikawa, Tetsuhiro Masaki, Fujimi Kawai, Erika Ota, Nobuyoshi Mori
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Early antibiotic discontinuation has been proposed in patients with hematologic malignancy with fever of unknown origin during febrile neutropenia (FN). But its safety and efficacy have been under discussion. Aims: We conducted a systematic review to compare the short- and long-term duration of antibiotics for FN. Methods: Two reviewers independently searched for articles from Embase, PubMed Central, and MEDLINE. The selection criteria were clinical trials comparing short- and long-term duration for FN in patients with hematologic malignancies and evaluating mortality, clinical failure, and bacteremia. Risk ratios (RR) with 95% confidence intervals (CIs) were calculated. Results: Eleven randomized controlled trials (RCTs) were included from 1977 to 2022. No significant differences in mortality (RR 1.43, 95% CI, 0.81, 2.53, I2 = 0), clinical failure (RR 1.14, 95% CI, 0.86, 1.49, I2 = 25), and bacteremia (RR 1.32, 95% CI, 0.87, 2.01, I2 = 34) were observed. We also evaluated the Grades of Recommendations, Assessment, Development and Evaluations for mortality, clinical failure, and bacteremia in the RCTs and found very low certainty of evidence. These outcomes may indicate that long-term duration of treatment is preferable. Summary/Conclusion: We could make no strong conclusions on the safety and efficacy of antimicrobial discontinuation before neutropenia resolution with FN. But the background of each study was different and our results are of low evidence and certainty. We need further, more evidential, RCTs.Keywords: Fever, Neutropenia, Febrile neutropenia, Infection